The main objective of this Head Injury Clinical and Laboratory Research Center is to establish a system whereby rational and improved therapies for patients with head injury can be defined, developed and tested scientifically. The proposed program will (1) define the physiological, morphological, metabolic and psychosocial sequelae of head injury in man; (2) collect, assemble and analyze data from head injured patients to formulate an accurate prognosis; (3) define in a well controlled animal model the anatomical, physiological and biochemical effects of injury on brain parenchyma and blood vessels and on systemic function. The influence of systemic insults to the injured brain will be studied in man and in animal models. Evaluations will be made in humans of therapy for brain acidosis, elevated intracranial pressure, ischemic and hyperemic cerebral blood flows, neurophysiological status, and post traumatic mental depression. The role of iatrogenic hypocapnic alkalosis in the management of patients will be clarified. The unifying hypothesis to be tested is that the brain parenchyma and its intrinsic vasculature can sustain reversible injury. These tissue elements can be rendered dysfunctional; yet, such dysfunction does not implicate irreversible disruption. The dysfunctional state may be temporary and if the internal milieu is appropriate for healing, the cells can recover. Dysfunction may be represented by reduced, excessive or aberrant metabolism. An animal intensive care unit and a controlled brain injury model provide the experimental environment. Acute and chronic animal studies will be conducted on morphologic neural and vascular changes, brain glucose utilization, cerebral microcirculation, the brain arachiconic acid cascade, regional cerebral blood flow and surface brain energy metabolism following controlled brain injury. Therapy will be tested by studying cerebral acidosis and treatment with THAM. We seek to understand the fundamental basis of neuronal loss after injury, and, by intervention to reverse this process.